CLINICAL PEARLS from the 2006 Annual Session of  American College of Physicians

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Case 1. A 68- year-old patient requests your advice on osteoporosis prevention. She brings with her reports from two prior dual energy x-ray absorptiometry (DXA) scans. She was started on alendronate in 2004 after the first scan. She walks 3 miles outdoors four times a week and does strength trainin

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CLINICAL PEARLS from the 2006 Annual Session of American College of Physicians

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1. CLINICAL PEARLS from the 2006 Annual Session of American College of Physicians

2. Case 1 A 68- year-old patient requests your advice on osteoporosis prevention. She brings with her reports from two prior dual energy x-ray absorptiometry (DXA) scans. She was started on alendronate in 2004 after the first scan. She walks 3 miles outdoors four times a week and does strength training twice a week. She drinks two glasses of milk every day. She does not drink alcohol or smoke. PMH: Menopause, age 52; No prior fractures Medications: Alendronate 35 mg once weekly on an empty stomach, Calcium 1000 mg daily, Multivitamin Family History: Mother had hip fracture at 72 DXA Results for Femur Neck: 2004 Total femur BMD = 0.820 g/cm2, T-score = -1.5 2005 Total femur BMD = 0.796 g/cm2, T-score = -1.7 Absolute change in BMD = 0.024 g/cm2 Least significant change for femur = 0.039 g/cm2; 95% confidence level

3. Question What would you recommend for this patient? A. Continue current therapy B. Measure 25-Hydroxy vitamin D C. Increase calcium to 1500 mg daily D. Increase alendronate to 70mg weekly E. Change to an alternative bisphosphonate

4. Discussion This case raises 3 questions that frequently arise in the diagnosis and management of osteopenia: when to treat, how to monitor treatment, and when to change or add an agent? In this case, treatment was initiated in a patient with one major risk factor for osteoporosis (mother’s history of hip fracture). The National Osteoporosis Foundation’s recommendation to initiate therapy at BMD T scores below -1.5 by hip DXA in a woman with one or more risk factors, or below -2.0 in a woman with no risk factors. The Foundation also recommends that repeat bone mineral density measurements for monitoring disease progression in response to therapy should generally be performed after 1 or 2 years. However, errors in the interpretation of serial measurements are common and result primarily from attributing clinical significance to a change in BMD that does not represent a true change. Precision error, the variability between multiple measurements, is an inherent limitation of any test, including DXA. Precision error in DXA measurements results from intra-operator and intra-machine variability.

5. Discussion The International Society for Clinical Densitometry recommends that each DXA facility determine its precision error at any given skeletal site: the magnitude of the change in bone density that signifies real biological change can then be determined. This is called the Least Significant Change (LSC) and is usually expressed as an absolute value (g/cm2) with a 95 percent level of confidence. Because both the LSC and absolute BMD values are reported in g/cm2, only absolute BMD values, not T scores, should be used for serial comparisons. An absolute change in BMD greater than the LSC likely represents a real change in BMD. However, an absolute change in BMD that is less than the LSC is not clinically significant. Such a change is due to precision error and not to treatment failure.

6. Discussion The absolute change in BMD in this case (0.024 g/cm2) is less than the LSC (0.039 gm/cm2). So, there has been no true change in BMD between 2004 and 2005. So, no change in treatment is warranted. Because there is no true change in BMD, there is no reason to suspect secondary causes of osteoporosis such as vitamin D deficiency. This patient is already getting adequate calcium intake through a combination of dietary intake and supplements. There are no data to suggest that increasing the dose of alendronate or changing to an alternative bisphosphonate would reduce her fracture risk further.

7. Clinical pearl Serial DXA measurements should be evaluated in the context of the least significant change in absolute bone mineral density.

8. Case 2 A 66-year-old male, retired mail carrier presents with vague epigastric abdominal pain of three months’ duration. He complains of a 20-pound weight loss and painless jaundice. Past medical history: Sjögren’s syndrome. Social history: Denies cigarettes or alcohol. Medications none. Review of systems: Increased urinary frequency and thirst. Complains of dry eyes and dry mouth. Physical examination: Ill-appearing male. Jaundiced. Abdomen: No palpable masses. Lymphatic system: No palpable lymphadenopathy. Laboratory tests: Hb 15.5 g/dL Alkaline phosphatase 520 u/L Total bilirubin 10 mg/dL Direct bilirubin 8.7 mg/dL Glucose 310 mg/dL ANA Positive Anti-SSA/SSB Positive Ultrasound Irregular mass, head of the pancreas CT scan Generalized enlargement of the pancreas with a “sausage shape” ERCP Segmental narrowing of the pancreatic duct with stenosis of the bile duct within the head of the pancreas

9. Question The next step in the management of this patient is: A. Obtain IgG subtypes (IgG type 4) B. Bile duct stenting C. PET scan D. CT directed biopsy of the pancreas E. Surgical consultation for Whipple procedure

10. Answer A. Obtain IgG subtypes (IgG type 4)

11. Discussion Autoimmune pancreatitis is a newly described type of chronic pancreatitis which may present with a clinical picture suggesting pancreatic cancer. AIP is associated with hypergammaglobulinemia, diffuse enlargement of the pancreas, irregular main pancreatic duct and the presence of autoantibodies such as ANA. Serum IgG4 accounts for only 5% of the total IgG4 in healthy subjects but is elevated in patients with AIP. Using a cutoff of 135mg/dl, the sensitivity and specificity of the serum IgG for distinguishing AIP from pancreatic cancer is 95 and 97 per cent. It is associated with other autoimmune diseases most commonly Sjogren’s syndrome, as well as with ulcerative colitis, primary sclerosing cholangitis and SLE.

12. Discussion Autoimmune pancreatitis has been described morphologically as a lymphoplasmacytic sclerosing pancreatitis. Ductal and periductal inflammatory infiltration composed of lymphocytes, plasma cells, and granulocytes causes narrowing, obstruction, and destruction of the pancreatic duct. The intrapancreatic segment of the common bile duct is commonly strictured. Patients with AIP often respond to a treatment course of corticosteroids with improvement of pancreatic and bile duct strictures, enlargement of the pancreas, and fall in the IgG 4 levels.

13. Clinical Pearl Consider AIP in patients presenting with idiopathic chronic pancreatitis or a clinical picture of pancreatic cancer. Finding serologic abnormalities such as positive autoantibodies and an elevated IgG subclass 4 may prevent an unnecessary Whipple procedure. This condition is often seen in individuals who suffer from Sjögren’s syndrome, primary sclerosing cholangitis, Crohn’s disease, chronic ulcerative colitis, systemic lupus erythematosus, Hashimoto’s thyroiditis, and retroperitoneal fibrosis

14. Case 3 A 54-year-old woman is being evaluated for labile BP and palpitations. She has a 2-year history of hypertension and is currently taking hydrochlorothiazide 25 mg daily and atenolol 50 mg daily. She also takes amitriptyline 50 mg nightly for fibromyalgia. She reports episodic spikes in BP as high as 180/110 mm Hg associated with palpitations. These episodes occur once or twice weekly and last for 30 to 45 minutes. They have occurred at any time of the day without any clear precipitating factors. Fractionated plasma free metanephrines are obtained to screen for pheochromocytoma. The results are as follows: metanephrine: < 0.20 nmol/L (normal <0.20 nmol/L) normetanephrine: 1.17 nmol/L (normal <0.90 nmol/L)

15. Question What is the next most appropriate step in the evaluation or treatment of this patient? A. Order an MIBG scan. B. Discontinue atenolol and order repeat fractionated plasma free metanephrines. C. Order a 24-hour urine for metanephrines and catecholamines. D. Discontinue amitriptyline and order repeat fractionated plasma free metanephrines. E. Order a CT scan of the abdomen

16. Answer D. Discontinue amitriptyline and order repeat fractionated plasma free metanephrines.

17. Discussion Pheochromocytomas are rare but clinically important tumors that if undetected, can be associated with unexpected, severe and occasionally lethal complications. The diagnosis depends on biochemical evidence of excess catecholamine production by the tumor. This is best accomplished by measuring metanephrine and normetanephrine concentrations in the plasma or urine. Due to superior sensitivity, measurement of fractionated plasma free metanephrines is considered by many to be the screening test of choice for pheochromocytoma. Because the prevalence of pheochromocytoma is low among patients screened for this disorder, false positive results greatly exceed true-positive results.

18. Discussion What are the common causes for false-positive test results and how to distinguish true-from falsepositive results? Tricyclic antidepressants (increase normetanephrine) are the most common drugs associated with false-positive plasma screening results. Other causes of false –positive results with plasma screening include use of beta-blockers (increase metanephrine), phenoxybenzamine (increase normetanephrine), catecholamine containing drugs (e.g., decongestants), and states of withdrawal from clonidine or related drugs, benzodiazepines or ethanol. Elevations of plasma free metanephrine or normetanephrine >3.5 times the upper limits of normal indicate a high probability of disease and justify imaging to locate the tumor. Lesser elevations indicate the possibility of disease but sources for a false positive result should be considered first.

19. Discussion If these conditions apply, plasma metanephrines should be repeated after elimination of the medication or other suspected cause of a positive result. If metanephrines remain elevated, additional tests can be considered. These include determination of the ratios of plasma metanephrine-to-epinephrine and normetanephrine-to-norepinephrine. High values of the ratios (>4.2 for metanephrine-to-epinephrine or >0.52 for normetanephrine-to-norepinephrine) suggest disease and imaging studies should be performed.

20. Clinical pearl False-positive results are more common than true-positive results when screening for pheochromocytoma. Concomitant drug therapy is often the cause.

21. Case 4 A 19-year-old male presents for follow-up after undergoing an endoscopic removal of meat impaction. The patient complains of intermittent episodes of dysphagia for solids that usually resolve with drinking a large volume of water. The patient denies pyrosis, reflux, regurgitation, odynophagia, nasal regurgitation, aspiration, or choking. Past medical history negative. Physical examination negative (no manifestations for CREST). Laboratory studies: Hb 16 g/dL WBC 7.8 x 10(9)/L; normal differential Sed rate 2 mm/hr ANA Negative EGD Minimal ringed appearance to the mucosa; no stricture, ulcer, Barrett’s epithelium, tumor, or obstruction

22. Question Which is the most likely diagnosis? A. Schatzki’s ring (non-obstructing) B. Diffuse esophageal spasm C. Eosinophilic esophagitis D. Achalasia E. Non-erosive reflux disease (NERD)

23. Answer C. Eosinophilic esophagitis

24. Discussion Eosinophilic esophagitis or allergic esophagitis, is a new disease with accelerating incidence and is characterized by eosinophilic infiltration of the esophagus due to allergic or idiopathic causes. Eosinophilic esophagitis should be considered in the differential diagnosis of young males, who otherwise do not have symptoms of GERD and have a history of solid food dysphagia with intermittent food impaction. Endoscopic findings are subtle and show a corrugated or “ringed” esophagus. Biopsies of the proximal and middle esophagus reveal increased intraepithelial (greater than 20 per high powered field) eosinophils. Treatment is topical corticosteroids. This patient does not have symptoms of diffuse esophageal spasm (pain), nor does the patient have symptoms to suggest nonerosive reflux disease, specifically, pyrosis, reflux, regurgitation. Achalasia is not a consideration in that the patient does not have symptoms of regurgitation or dysphagia for liquids.

25. Clinical Pearl Consider eosinophilic esophagitis as a cause for solid food dysphagia or food impaction in individuals with no other primary esophageal disorder.

26. Case 5 A 24-year-old female with a history of familial adenomatous polyposis presents with jaundice, pruritus, dark urine, and clay colored stool. The patient is a college student, who is returning from a semester abroad studying marine biology. Past medical history: Familial adenomatous polyposis. Past surgical history: Total colectomy with ileoanal pouch. Social history: Recent travel to Costa Rica. No hepatotoxic medications. Denies vitamin or herb use. No alcohol use. Denies drug use. No history of accidental needle stick, blood transfusion, or high risk behaviors. Physical examination: Skin: Café-au-lait spot right hip. Jaundice. No stigmata of chronic liver disease. Abdominal examination: Negative organomegaly. Rectal examination: Heme positive stool (stool appears silver). Laboratory studies: Alkaline phosphatase 800 u/L AST 92 u/L ALT 80 u/L Total bilirubin 6.7 mg/dL Direct bilirubin 5.4 mg/dL

27. Question The most likely cause for jaundice is: A. Ampullary tumor B. Metastatic colon cancer to the liver C. Acute viral hepatitis D. Hepatic parasite infection (worm) E. Primary sclerosing cholangitis

28. Answer A. Ampullary tumor

29. Discussion The basic molecular foundation for familial adenomatous polyposis (FAP) is a genetic mutation of the APC gene. The hallmark lesion of FAP is diffuse colonic polyposis with hundreds to thousands of polyps developing during adolescence. Without a prophylactic colectomy, colorectal cancer inevitably develops by age 40. These patients have an increased cancer risk, primarily in the periampullary regions of the duodenum and the retained rectal remnant of patients who have had a partial colectomy.

30. Clinical pearl Because there is a 5-10 percent lifetime risk of patients with FAP developing an ampullary carcinoma, all patients should undergo periodic upper GI screening with forward and sideviewing endoscopes. Screening should begin at age 21 with intervals of 3-5 years if no lesions are found.

31. Case 6 A 53-year-old woman is referred for evaluation of resistant hypertension. She has had high blood pressure for 8 years. There is a family history in her mother. BP averages 150/100 mm Hg despite current therapy which consists of hydrochlorothiazide 25 mg daily, lisinopril 40 mg daily, atenolol 50 mg daily and potassium chloride 20 mEq daily. She tolerates these medications well and is compliant with therapy. She attempts a low salt diet, is 10 pounds overweight and sedentary. She is a non-smoker, non-diabetic, and has no history of dyslipidemia. She has no history or symptoms of target organ injury. Examination disclosed a BP of 156/104 mm Hg. Pulse is 54 and regular. Other than mild obesity, the examination is normal. Laboratory studies include: creatinine 1.1 mg/dL, sodium 142 mEq/L, potassium 3.6 mEq/L (normal 3.6-4.8 mEq/L), glucose 89 mg/dL, cholesterol 180 mg/dL, triglycerides 160 mg/dL. Urinalysis is normal.

32. Question What is the next most appropriate step in the evaluation or treatment of this patient? A. Obtain a 24-hour ambulatory BP recording to rule out a white-coat effect. B. Increase hydrochlorothiazide to 50 mg daily. C. Evaluate for pheochromocytoma. D. Add amlodipine 5 mg daily. E. Evaluate for primary aldosteronism

33. Answer E. Evaluate for primary aldosteronism

34. Discussion Several considerations should be made when a patient presents with resistant hypertension. Among these is the possibility of a secondary cause of hypertension. Primary aldosteronism is now recognized as the most common treatable secondary cause of hypertension. This diagnosis should be considered in hypertensive patients with hypokalemia regardless of presumed cause. The widespread use of angiotensin-converting-enzyme inhibitors (ACEIs) and angiotensinreceptor blockers (ARBs) has uncovered a group of patients at increased risk for this disorder.

35. Discussion Because ACEIs and ARBs inhibit aldosterone production, their use is associated with and increase in plasma potassium level and thus, hypokalemia is quite uncommon. Therefore, low plasma potassium or the need for potassium supplements in patients taking full doses of an ACEI or an ARB, with or without concomitant diuretic therapy, is a tip-off to the possibility of primary aldosteronism. Further evaluation should include screening for this disorder by determining the ratio of plasma aldosterone concentration to plasma renin activity which has fair diagnostic accuracy.

36. Clinical pearl Primary aldosteronism is the most common treatable secondary cause of hypertension and should be considered in the hypokalemic hypertensive patient regardless of presumed cause.

37. Case 7 A 38-year-old presents for evaluation of tightening of the skin in both arms and legs of 12 weeks duration. He considered himself in otherwise good health and took no medication or supplements. He had just begun a strenuous exercise program about one month prior to onset of symptoms. He first noticed the sudden onset of swelling in his arms and legs which resolved gradually and was left with tight bound down skin. There was no history of Raynaud’s, tick bites, or psoriasis. Physical examination revealed induration of the skin from the ankle to mid thigh and mid hand to just above the elbow. There was decreased ROM of the wrist, ankle and elbow. Muscle strength was normal.

38. Case 7 Laboratory studies: Hb 15.2 g/dl WBC 8,700/ul % Eosinophils 12 % Creatinine 0.9 UA normal ANA 1:40 RF negative CK 250 (normal < 175) Sed rate 62 mm/hr

39. Question Which one of the following is the most likely diagnosis? A. Eosinophilic fasciitis B. Scleroderma C. Systemic lupus erythematosis D. Polymyositis E. Idiopathic Hypereosinophilic Syndrome

40. Answer A. Eosinophilic fasciitis

41. Discussion Eosinophilic fasciitis usually presents fairly suddenly with diffuse swelling in the extremities. Over time the edema subsides and the skin can become very indurated and can mimic scleroderma, although it may spare the hands and feet. Patients do not have a history of Raynaud’s phenomenon in contrast to scleroderma. Laboratory manifestations include eosinophilia, elevated sedimentation rate, and a polyclonal gammopathy. There can be perimysial inflammation that can cause a slightly elevated aldolase or CK level. Treatment with prednisone is beneficial. A full thickness biopsy to include fascia is needed to make the diagnosis.

42. Discussion Patients with scleroderma will have tight bound skin of their fingers and skin proximal to the MCP joints. Also, most patients will have Raynaud’s phenomenon. Although, the patient had a weakly positive ANA, they did not have any other clinical manifestations to suggest lupus. Polymyositis usually causes proximal muscle weakness without pain, but is not associated with swelling of the extremities, and therefore would be unlikely in this case. Patients with the Hypereosinophilic Syndrome have other internal organ involvement including cardiac, pulmonary, liver, and central and peripheral nervous system. While skin involvement can be seen it usually causes angioedema and urticarial lesions or pruritic, erythematous papules and nodules. Fasciitis is not seen.

43. Clinical pearl Eosinophilic fasciitis can mimic scleroderma, but patients do not have Raynaud’s. Differentiation from scleroderma is important because eosinophilic fasciitis is steroid responsive.

44. Case 8 A 67-year-old female is referred for evaluation and treatment for refractory lymphocytic colitis. The patient complains of watery diarrhea for the past three months. The patient was initially treated with Imodium with a good response but symptoms recurred on discontinuing therapy. The patient was then treated with a 5-ASA product, which worsened her symptoms. Recently the patient has been receiving budesonide and Imuran with good improvement in her symptoms. However, she does suffer with severe osteopenia and her physician is concerned regarding her long-term steroid use. In addition, the patient is concerned about the side effect profile of azathioprine and presents for an opinion regarding further evaluation and treatment. Presently the patient complains of three loose watery stools per day. Past medical history: Hypothyroidism, hypertension, osteopenia. Medications: Fosamax 70 mg per week, hydrochlorothiazide 25 mg daily, Synthroid 0.175 mg daily. Allergies none.

45. Case 8 Physical examination: Elderly, thin white female in no acute distress. Conjunctiva pale. Physical examination otherwise unremarkable. Laboratory studies: Hb 10 g/dLs MCV 80 fL Alb 3.1 g/dL Iron 10 mcg/dL TIBC 410 mcg/dL Ferritin 6 Screening colonoscopy 2004 Negative Flexible sigmoidoscopy three months ago Positive for lymphocytic colitis Flexible sigmoidoscopy during the present evaluation Negative for microscopic colitis

46. Question The next step in the management of this patient is: A. Repeat colonoscopy with right colon biopsies B. EGD with small bowel biopsy C. Initiate Pepto-Bismol therapy D. Discontinue Fosamax E. Encourage the patient to continue long-term budesonide therapy

47. Answer B. EGD with small bowel biopsy

48. Discussion Microscopic colitis typically presents in the 6th to 8th decade with a female predominance of 9:1. Microscopic colitis is associated with a watery diarrhea without fever, dehydration, nausea, vomiting, or GI hemorrhage. In this patient with microscopic colitis, iron deficiency anemia, and osteopenia, one needs to consider celiac sprue as an associated condition contributing to her continued diarrhea. Patients with microscopic colitis can have sprue-like changes in the small bowel in 2-15 percent of the cases.

49. Clinical pearl Microscopic colitis and celiac sprue often coexist. Celiac disease should be excluded in all patients with microscopic colitis, particularly if diarrhea does not respond to conventional therapy.

50. Case 9 A 67-year-old female presents with chest pain and dyspnea. The pain began in the morning while trying to free her dog whose foot was caught in a raccoon trap. ECG: Sinus rhythm with a heart rate of 85, ST-segment elevation in leads V2-V4, T-wave inversions in the anterior leads, and a prolonged QT interval. Labs: Peak Troponin T 0.47 ng/ml (normal < 0.03 ng/ml). Peak Creatine kinase-MB 16.5 ng/ml (normal < 6.2 ng/ml) Echocardiogram on Day of Admission: EF 32% with moderate hypokinesis in the mid ventricle segments and apical akinesis. Regional wall motion abnormalities extend beyond the vascular distribution of a single coronary artery. Coronary angiogram: 25% stenosis in the mid LAD without evidence of plaque rupture, no angiographic evidence of epicardial spasm. Echocardiogram on Day 7: EF 63% with no regional wall motion abnormalities.

51. Question What is the likely etiology of this patient’s chest pain? A. Pulmonary embolism B. Left ventricular apical ballooning syndrome C. Hyperventilation syndrome D. Left anterior descending thrombus E. Idiopathic dilated cardiomyopathy

52. Answer B. Transient left ventricular apical ballooning syndrome

53. Discussion Transient left ventricular (LV) apical ballooning syndrome is a form of acute, reversible LV dysfunction that most commonly occurs following intense emotional or physiologic stress. The syndrome was initially reported in Japan and described as “takotsubo” cardiomyopathy, a reference to the narrow-necked fishing pot used to trap octopus that resembles the ballooning of the LV during systole. Patients generally present with ECG changes suggestive of acute myocardial infarction in the absence of obstructive coronary artery disease or plaque rupture. A hallmark of the syndrome is reversible wall motion abnormalities at the LV apex and midventricle that do not correlate with a single-vessel distribution.

54. Discussion Cardiac enzyme levels are typically mildly elevated. These patients have markedly higher catecholamine levels than patients presenting with myocardial infarction: this lends support to a proposed mechanism of catecholamine-mediated myocardial stunning. This syndrome is seen almost exclusively in post-menopausal women, although the basis for this predilection is unknown. Resolution of left ventricular dysfunction is observed usually within 7 to 14 days. Recurrence rates appear to be low based on preliminary data. Pulmonary embolus can result in a mild troponin elevation but would not explain the LV wall motion abnormalities. Hyperventilation syndrome may cause chest pain and dyspnea, but would not lead to regional wall motion abnormalities. Although the electrocardiographic findings could be consistent with a thrombus in the left anterior descending artery, there was no evidence of thrombus on angiogram. Idiopathic dilated cardiomyopathy does not resolve quickly and does not present acutely with chest pain.

55. Clinical pearl Emotional or physiologic stress can precipitate severe, reversible LV dysfunction in postmenopausal women without coronary disease.

56. Case 10 A 52-year-old presents for routine annual exam. Pap smear report notes atypical glandular cells not otherwise specified.

57. Question What is the best next step in the management of the Pap smear findings? A. Reassure patient that this is a common finding in the first years after menopause B. Repeat Pap smear now with HPV typing C. Treat with estrogen vaginal cream and repeat Pap smear in six weeks D. Refer to gynecologist for colposcopy, directed cervical biopsy, endocervical curettage, and endometrial biopsy E. Hysterectomy

58. Discussion Cervical cytology is primarily a screening test for squamous epithelial lesions and squamous cancer and is unreliable for the evaluation of suspected endometrial abnormalities. Nevertheless, endometrial (glandular) cells are sometimes detected on cervical cytology and have important implications. The Bethesda System created a standard terminology for reporting cervical cytology results. The system differentiates Atypical Squamous Cells (ASC), including the subcategory of atypical squamous cells of undetermined significance (ASC-US), from Atypical Glandular Cells (AGC).

59. Discussion Approximately 250,000 women are diagnosed with AGC annually inthe United States. The finding of AGC is less common than ASC-US but is associated with a much greater risk of underlying malignant or premalignant lesions: 10% to 39% will have a high-grade lesion on histologic examination. While most of these lesions prove to be high-grade squamous lesions of the cervix, up to 8% of women with AGC are found to have endometrial cancer. Consensus guidelines published in 2001 recommend that women with AGC undergo colposcopy, directed cervical biopsy, and endocervical curettage. For women over 35, endometrial biopsy should also be done. While HPV DNA testing may be a useful screening test in the initial evaluation of AGC, it is not considered sufficient in the evaluation of AGC.

60. Discussion Treatment with estrogen vaginal cream followed by repeat Pap smear would be a reasonable option only if this patient was post-menopausal and found to have ASC-US: ASC-US in postmenopausal women not on hormone therapy may be due to reactive changes in the cervical mucosa as a result of estrogen loss. Hysterectomy following a diagnosis of AGC would be necessary only if a gynecologic cancer is confirmed on further evaluation.

61. Clinical pearl The finding of AGC on a Pap smear should prompt referral to a gynecologist for colposcopy directed cervical biopsy, and endocervical curettage. For women over 35, endometrial biopsy should also be done

62. A Reminder of the previous CLINICAL PEARLS

63. Osteoporosis Serial DXA measurements should be evaluated in the context of the least significant change in absolute bone mineral density.

64. Pancreatic Cancer Consider AIP in patients presenting with idiopathic chronic pancreatitis or a clinical picture of pancreatic cancer. Finding serologic abnormalities such as positive autoantibodies and an elevated IgG subclass 4 may prevent an unnecessary Whipple procedure.

65. Pheochromocytoma False-positive results are more common than true-positive results when screening for pheochromocytoma. Concomitant drug therapy is often the cause.

66. Dysphagia Consider eosinophilic esophagitis as a cause for solid food dysphagia or food impaction in individuals with no other primary esophageal disorder.

67. FAP Because there is a 5-10 percent lifetime risk of patients with FAP developing an ampullary carcinoma, all patients should undergo periodic upper GI screening with forward and sideviewing endoscopes. Screening should begin at age 21 with intervals of 3-5 years if no lesions are found.

68. Hypertension Primary aldosteronism is the most common treatable secondary cause of hypertension and should be considered in the hypokalemic hypertensive patient regardless of presumed cause.

69. Eosinophilic Fasciitis Eosinophilic fasciitis can mimic scleroderma, but patients do not have Raynaud’s. Differentiation from scleroderma is important because eosinophilic fasciitis is steroid responsive.

70. Transient LV Apical Ballooning Syndrome Emotional or physiologic stress can precipitate severe, reversible LV dysfunction in postmenopausal women without coronary disease.

71. Microscopic Colitis Microscopic colitis and celiac sprue often coexist. Celiac disease should be excluded in all patients with microscopic colitis, particularly if diarrhea does not respond to conventional therapy.

72. AGC on Pap Smear The finding of AGC on a Pap smear should prompt referral to a gynecologist for colposcopy directed cervical biopsy, and endocervical curettage. For women over 35, endometrial biopsy should also be done

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